Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

Alfaxalone or ketamine‐medetomidine in cats undergoing ovariohysterectomy: a comparison of intra‐operative parameters and post‐operative pain

ObjectiveTo compare post-operative pain in cats after alfaxalone or ketamine- medetomidine anaesthesia for ovariohysterectomy (OHE) and physiologic parameters during and after surgery.Study designProspective ‘blinded’ randomized clinical study.AnimalsTwenty-one healthy cats.MethodsCats were assigned randomly into two groups: Group A, anaesthesia was induced and maintained with alfaxalone [5 mg kg^?1 intravenously (IV) followed by boli (2 mg kg^?1 IV); Group MK, induction with ketamine (5 mg kg^?1 IV) after medetomidine (30 μg kg^?1 intramuscularly (IM)], and maintenance with ketamine (2 mg kg^?1 IV). Meloxicam (0.2 mg kg^?1 IV) was administered after surgery. Basic physiological data were collected. At time T = -2, 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours post-operatively pain was assessed by three methods, a composite pain scale (CPS; 0–24 points), a visual analogue scale (VAS 0–100 mm), and a mechanical wound threshold (MWT) device. Butorphanol (0.2 mg kg^?1 IM) was administered if CPS was scored =13. Data were analyzed using a general linear model, Kruskal–Wallis analyses, Bonferroni-Dunn test, unpaired t-test and Fisher's exact test as relevant. Significance was set at p < 0.05.ResultsVASs were significantly higher at 0.5, 1, 2, 4, and 20 hours in group A; MWT values were significantly higher at 8 and 12 hours in group MK. Post-operative MWT decreased significantly compared to baseline in both groups. There was no difference in CPS at any time point. Five cats required rescue analgesia (four in A; one in MK).Conclusion and clinical relevanceAnaesthesia with ketamine-medetomidine was found to provide better post-surgical analgesia than alfaxalone in cats undergoing OHE; however, primary hyperalgesia developed in both groups. Alfaxalone is suitable for induction and maintenance of anaesthesia in cats undergoing OHE, but administration of additional sedative and analgesic drugs is highly recommended.     

Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine

ObjectiveTo describe alfaxalone total intravenous anaesthesia (TIVA) following premedication with buprenorphine and either acepromazine (ACP) or dexmedetomidine (DEX) in bitches undergoing ovariohysterectomy.Study designProspective, randomised, clinical study.AnimalsThirty-eight healthy female dogs.MethodsFollowing intramuscular buprenorphine (20 μg kg^?1) and acepromazine (0.05 mg kg^?1) or dexmedetomidine (approximately 10 μg kg^?1, adjusted for body surface area), anaesthesia was induced and maintained with intravenous alfaxalone. Oxygen was administered via a suitable anaesthetic circuit. Alfaxalone infusion rate (initially 0.07 mg kg^?1 minute^?1) was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Alfaxalone boluses were given if required. Ventilation was assisted if necessary. Alfaxalone dose and physiologic parameters were recorded every 5 minutes. Depth of sedation after premedication, induction quality and recovery duration and quality were scored. A Student's t-test, Mann–Whitney U and Chi-squared tests determined the significance of differences between groups. Data are presented as mean ± SD or median (range). Significance was defined as p < 0.05.ResultsThere were no differences between groups in demographics; induction quality; induction (1.5 ± 0.57 mg kg^?1) and total bolus doses [1.2 (0 – 6.3) mg kg^?1] of alfaxalone; anaesthesia duration (131 ± 18 minutes); or time to extubation [16.6 (3–50) minutes]. DEX dogs were more sedated than ACP dogs. Alfaxalone infusion rate was significantly lower in DEX [0.08 (0.06–0.19) mg kg^?1 minute^?1] than ACP dogs [0.11 (0.07–0.33) mg kg^?1 minute^?1]. Cardiovascular variables increased significantly during ovarian and cervical ligation and wound closure compared to baseline values in both groups. Apnoea and hypoventilation were common and not significantly different between groups. Arterial haemoglobin oxygen saturation remained above 95% in all animals. Recovery quality scores were significantly poorer for DEX than for ACP dogs.Conclusions and clinical relevanceAlfaxalone TIVA is an effective anaesthetic for surgical procedures but, in the protocol of this study, causes respiratory depression at infusion rates required for surgery.     

A comparison of the efficacy and cardiorespiratory effects of four medetomidine-based anaesthetic protocols in the red fox (Vulpes vulpes)

ObjectiveTo evaluate the anaesthetic and cardiorespiratory effects of four anaesthetic protocols in red foxes (Vulpes vulpes).Study designProspective, blinded and randomized complete block design.AnimalsTen adult captive red foxes.MethodsFoxes were anaesthetized by intramuscular (IM) injection using four protocols in random order: medetomidine 40 μg kg^?1, midazolam 0.3 mg kg^?1 and butorphanol 0.1 mg kg^?1 (MMiB), medetomidine 40 μg kg^?1 and ketamine 4 mg kg^?1 (MK40/4), medetomidine 60 μg kg^?1 and ketamine 4 mg kg^?1 (MK60/4), medetomidine 40 μg kg^?1 and tiletamine/zolazepam 2 mg kg^?1 (MTZ). Time to lateral recumbency, induction time and time to recovery following IM administration of atipamezole 0.2 mg kg^?1 were recorded. Heart rate (HR), respiratory rate (_fR) and rhythm, blood pressure, rectal temperature, end-tidal CO₂ tension (Pe′Co₂), functional oxygen saturation and presence/absence of interdigital, palpebral and ear reflexes were recorded every 10 minutes, and following administration of atipamezole. Data were analysed using two-way repeated-measures anova with Bonferroni post tests; p < 0.05 was considered significant.ResultsAll protocols produced profound sedation with good muscle relaxation. Only the MMiB protocol diverged significantly from the others. Induction of anaesthesia and recovery time following atipamezole were significantly longer, and f_R and initial HR significantly lower with MMiB than with the other protocols. With all protocols, mean arterial blood pressure (MAP) was initially relatively high (140–156 mmHg), and decreased significantly over time. With all protocols, the administration of atipamezole resulted in a rapid, significant decrease in MAP and an increase in HR.Conclusions and clinical relevanceAll four protocols provided anaesthetic conditions suitable for minor procedures and allowed endotracheal intubation. The cyclohexanone protocols provided quicker and more reliable inductions and recoveries than the MMiB protocol.     

Effects of different doses of dexmedetomidine on anaesthetic induction with alfaxalone – a clinical trial

ObjectiveTo document the effects of two doses of dexmedetomidine on the induction characteristics and dose requirements of alfaxalone.Study designRandomized controlled clinical trial.AnimalsSixty one client owned dogs, status ASA I-II.MethodsDogs were allocated randomly into three groups, receiving as pre-anaesthetic medication, no dexmedetomidine (D₀), 1 μg kg^?1 dexmedetomidine (D₁) intramuscularly (IM) or 3 μg kg^?1 dexmedetomidine IM (D₃). All dogs also received 0.2 mg kg^?1 methadone IM. Level of sedation was assessed prior to induction of anaesthesia. Induction of general anaesthesia was performed with alfaxalone administered intravenously to effect at a rate of 1 mg kg^?1 minute^?1; the required dose to achieve tracheal intubation was recorded. Anaesthesia was maintained with isoflurane in oxygen. Cardiopulmonary parameters were recorded throughout the anaesthetic period. Quality of intubation, induction and recovery of anaesthesia were recorded. Quantitative data were compared with one-way anova or Kruskal-Wallis test. Repeated measures were log-transformed and analysed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for categorical data, with exception of sedation level (p < 0.001). The doses (mean ± SD) of alfaxalone required for intubation were D₀ 1.68 ± 0.24, D₁ 1.60 ± 0.36 and D₃ 1.41 ± 0.43, the difference between D₀ and D₃ being statistically significant (p = 0.036). Heart and respiratory rates during the anaesthetic period were significantly different over time and between groups (p < 0.001); systolic arterial blood pressure was significantly different over time (p < 0.001) but not between groups (p = 0.833). Induction quality and recovery scores were similar between groups (p = 1.000 and p = 0.414, respectively).Conclusions and clinical relevanceThe administration of alfaxalone resulted in a good quality anaesthetic induction which was not affected by the dose of dexmedetomidine. Dexmedetomidine at 3 μg kg^?1 IM combined with methadone provides good sedation and enables a reduction of alfaxalone requirements.     

Effects of intramuscular alfaxalone alone or in combination with diazepam in swine

ObjectiveTo describe the use of intramuscular (IM) premedication with alfaxalone alone or in combination with diazepam in pigs.Study designRandomised‐controlled trial.AnimalsTwelve healthy 2 month‐old Landrace x Large White pigs weighing 21.3 ± 2.4 kg.MethodsAnimals were distributed randomly into two groups: group A (n = 6) 5 mg kg^?1 of IM alfaxalone; and group AD (n = 6) 5 mg kg^?1 of IM alfaxalone + 0.5 mg kg^?1 of IM diazepam mixed in the same syringe. The total volume of injectate was standardized at 14 mL by dilution in 0.9% sodium chloride. Pain on injection, the degree of sedation and the quality of and time to induction of recumbency were evaluated. Once pigs were recumbent, reflexes were evaluated. Pulse and respiratory rates and arterial oxygen saturation were recorded at 5 and 10 minutes after drug administration. Pigs were then moved to another room for subsequent anaesthesia.ResultsTwo animals of group A and one of group AD showed slight pain on drug injection. Time to lateral recumbency (in seconds) was shorter in group AD (mean 203 ± SD 45 range 140–260) than group A (302 ± 75, range 220–420; p < 0.05). In group AD sedation was deeper, and on recumbency there was better muscle relaxation. When moved for anaesthesia, two pigs in Group A showed slight resistance but did not vocalize. There were no differences in physiologic measurements between groups, although in both groups, respiratory rate was significantly lower at ten compared with five minutes post drug injection. There was no apneoa.Conclusions and clinical relevanceIM administration of alfaxalone combined with diazepam resulted in a rapid onset of recumbency and deep sedation, with minimal side effects. The combination might be useful for premedication, but volume of injectate will limit its use to small pigs.     

Intramuscular administration of alfaxalone in red‐eared sliders (Trachemys scripta elegans) – effects of dose and body temperature

ObjectiveTo characterise the effects of alfaxalone by intramuscular (IM) injection in red-eared slider turtles and the influence of body temperature on anaesthetic duration and depth.Study designProspective, randomised part-blinded experimental trial.AnimalsTen healthy adult female red-eared sliders.MethodsEach turtle was anaesthetized four times with 10 and 20 mg kg^?1 alfaxalone at 20 and 35 °C respectively. Time to maximal effect and plateau and recovery periods were recorded. Skeletal muscle tone, presence of various reflexes, response to noxious stimuli, and heart rate were assessed.ResultsResults are given for protocols 10 mg kg^?1 20 °C; 20 mg kg^?1 20 °C; 10 mg kg^?1 35 °C and 20 mg kg^?1 35 °C, respectively: mean time (±SD) to maximal effect was 16 ± 8, 19 ± 6, 5 ± 2 and 7 ± 5 minutes; duration of the plateau phase was 13 ± 12, 28 ± 13, 8 ± 5 and 8 ± 5 minutes and recovery time was 76 ± 20, 126 ± 17, 28 ± 9 and 41 ± 20 minutes. Endotracheal intubation was successful in 80%, 100%, 0% and 30% of turtles, respectively. At 35 °C, all animals retained nociceptive sensation in the front limbs, hind limbs and vent, whereas at 20 °C a few turtles lost peripheral nociceptive sensation. Corneal and tap reflexes were retained in all trials. Mean heart rates were 30 ± 2 and 66 ± 4 beats minute^?1 at 20 and 35 °C, respectively.Conclusions and clinical relevanceAlfaxalone administered IM in red-eared sliders provided smooth, rapid induction and uneventful recovery. At 35 °C either dosage provided only short (5–10 minutes) and light sedation. At 20 °C, 10 mg kg^?1 provided sedation suitable for short non-invasive procedures. About 20 mg kg^?1 provided anaesthesia of approximately 20 minutes duration, appropriate for induction of inhalational anaesthesia or for brief surgical procedures with supplemental analgesia.     

Comparison between three dosages of intramuscular alfaxalone and a ketamine–dexmedetomidine–midazolam–tramadol combination in golden-headed lion tamarins (Leontopithecus chrysomelas)

ObjectivesTo characterize the cardiopulmonary and anesthetic effects of alfaxalone at three dose rates in comparison with a ketamine–dexmedetomidine–midazolam–tramadol combination (KDMT) for immobilization of golden-headed lion tamarins (GHLTs) (Leontopithecus chrysomelas) undergoing vasectomy.Study designProspective clinical trial.AnimalsA total of 19 healthy, male, wild-caught GHLTs.MethodsTamarins were administered alfaxalone intramuscularly (IM) at 6, 12 or 15 mg kg^–1, or KDMT, ketamine (15 mg kg^–1), dexmedetomidine (0.015 mg kg^–1), midazolam (0.5 mg kg^–1) and tramadol (4 mg kg^–1) IM. Immediately after immobilization, lidocaine (8 mg kg^–1) was infiltrated subcutaneously (SC) at the incision site in all animals. Physiologic variables, anesthetic depth and quality of immobilization were assessed. At the end of the procedure, atipamezole (0.15 mg kg^–1) was administered IM to group KDMT and tramadol (4 mg kg^–1) SC to the other groups; all animals were injected with ketoprofen (2 mg kg^–1) SC.ResultsA dose-dependent increase in sedation, muscle relaxation and immobilization time was noted in the alfaxalone groups. Despite the administration of atipamezole, the recovery time was longer for KDMT than all other groups. Muscle tremors were noted in some animals during induction and recovery with alfaxalone. No significant differences were observed for cardiovascular variables among the alfaxalone groups, whereas an initial decrease in heart rate and systolic arterial blood pressure was recorded in KDMT, which increased after atipamezole administration.Conclusions and clinical relevanceAlfaxalone dose rates of 12 or 15 mg kg^–1 IM with local anesthesia provided good sedation and subjectively adequate pain control for vasectomies in GHLTs. KDMT induced a deeper plane of anesthesia and should be considered for more invasive or painful procedures. All study groups experienced mild to moderate hypothermia and hypoxemia; therefore, the use of more efficient heating devices and oxygen supplementation is strongly recommended when using these protocols.     

Alfaxalone anaesthesia in the green iguana (Iguana iguana)

ObjectiveTo characterise the anaesthetic effects of alfaxalone administered intramuscularly (IM) at 10, 20, and 30 mg kg^?1.Study designProspective, randomized cross-over study.AnimalsTen juvenile green iguanas (Iguana iguana) of mean body weight (±SD) 480 ± 134 g.MethodsAlfaxalone was administered IM in the triceps of both thoracic limbs. Times for anaesthetic induction, plateau and recovery periods were recorded. Skeletal muscle tone of the jaw, neck, thoracic limbs, pelvic limbs, and tail was scored. The palpebral, corneal and righting reflexes, and the response to painful stimuli were also assessed. Pulse rate and respiratory rate were recorded. Comparisons between different dosages and over time were made using anova.ResultsTimes are given for 10, 20 and 30 mg kg^?1 dosages respectively: mean time to maximal effect was 7.7 ± 2.2, 5.4 ± 1.7 and 3.9 ± 1.2 minutes; duration of the plateau phase was 11.3 ± 3.8, 22.1 ± 6.5 and 39.1 ± 11.5 minutes; recovery time was 10 ± 2.4, 17.5 ± 8.6 and 25 ± 7.1 minutes; and total anaesthetic duration was 29 ± 35.7, 45 ± 8.2 and 68 ± 9.8 minutes. Endotracheal intubation was possible in 40% of the subjects given 10 mg kg^?1 and in 100% subjects given both 20 and 30 mg kg^?1. Loss of response to a painful stimulus was seen in 0/10, 8/10 and 9/10 animals at 10, 20, and 30 mg kg^?1 respectively. There was an initial dose-dependent depression of respiration followed by a significant increase in frequency over time. In contrast, pulse rates decreased by 20% over the duration of the anaesthetic events.Conclusions and clinical relevanceIntramuscular administration of alfaxalone is a simple, rapid and reliable means of achieving relatively brief sedation or anaesthesia in healthy green iguanas. A dosage of 10 mg kg^?1 provides light sedation, appropriate for examination and venipuncture; 20 mg kg^?1 provides a level suitable for minor procedures or for endotracheal intubation and supplementation with inhalational anaesthesia; 30 mg kg^?1 produces an anaesthetic plane suitable for surgical procedures of limited duration (up to 40 minutes).     

Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats

ObjectiveTo compare the effects of propofol and alfaxalone on respiration in cats.Study designRandomized, ‘blinded’, prospective clinical trial.AnimalsTwenty cats undergoing ovariohysterectomy.MethodsAfter premedication with medetomidine 0.01 mg kg⁻¹ intramuscularly and meloxicam 0.3 mg kg⁻¹ subcutaneously, the cats were assigned randomly into two groups: group A (n = 10) were administered alfaxalone 5 mg kg⁻¹ minute⁻¹ followed by 10 mg kg⁻¹ hour⁻¹ intravenously (IV) and group P (n = 10) were administered propofol 6 mg kg⁻¹ minute⁻¹ followed by 12 mg kg⁻¹hour⁻¹ IV for induction and maintenance of anaesthesia, respectively. After endotracheal intubation, the tube was connected to a non-rebreathing system delivering 100% oxygen. The anaesthetic maintenance drug rate was adjusted (± 0.5 mg kg⁻¹ hour⁻¹) every 5 minutes according to a scoring sheet based on physiologic variables and clinical signs. If apnoea > 30 seconds, end-tidal carbon dioxide (Pe′CO₂) > 7.3 kPa (55 mmHg) or arterial haemoglobin oxygen saturation (SpO₂) < 90% occurred, manual ventilation was provided. Methadone was administered postoperatively. Data were analyzed using independent-samples t-tests, Fisher's exact test, linear mixed-effects models and binomial test.ResultsManual ventilation was required in two and eight of the cats in group A and P, respectively (p = 0.02). Two cats in both groups showed apnoea. Pe′CO₂ > 7.3 kPa was recorded in zero versus four and SpO₂ < 90% in zero versus six cats in groups A and P respectively. Induction and maintenance dose rates (mean ± SD) were 11.6 ± 0.3 mg kg⁻¹ and 10.7 ± 0.8 mg kg⁻¹ hour⁻¹ for alfaxalone and 11.7 ± 2.7 mg kg⁻¹ and 12.4 ± 0.5 mg kg⁻¹ hour⁻¹ for propofol.Conclusion and clinical relevanceAlfaxalone had less adverse influence on respiration than propofol in cats premedicated with medetomidine. Alfaxalone might be better than propofol for induction and maintenance of anaesthesia when artificial ventilation cannot be provided.     

Medetomidine/midazolam/ketamine anaesthesia in ferrets: effects on cardiorespiratory parameters and evaluation of plasma drug concentrations

ObjectiveTo evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo).Study designProspective randomized experimental study.AnimalsEighteen adult ferrets: weight median 1.19 (range 0.81–1.60) kg.MethodsAnimals were allocated to one of three groups: group IM07 received 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 7 mg kg^?1 ketamine IM; group IM10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine IM; and group SC10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5–T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p < 0.05 was considered significant.ResultsResults are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute^?1, decreasing with time. PaO₂ (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L^?1 for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10.Conclusions and clinical relevanceMMK combinations containing either 7 or 10 mg kg^?1 ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.     

Alfaxalone induction dose following administration of medetomidine and butorphanol in the dog

ObjectiveTo determine in dogs the effects of medetomidine and butorphanol, alone and in combination, on the induction dose of alfaxalone and to describe the induction and intubation conditions.Study designProspective, randomized, blinded clinical trial.AnimalsEighty-five client-owned dogs (ASA 1 or 2).MethodsSubjects were block randomized to treatment group according to temperament. The treatment groups were: medetomidine 4 μg kg^?1 (M), butorphanol 0.1 mg kg^?1 (B), or a combination of both (MB), all administered intramuscularly. After 30 minutes, a sedation score was assigned, and alfaxalone 0.5 mg kg^?1 was administered intravenously over 60 seconds by an observer who was unaware of treatment group. Tracheal intubation conditions were assessed and, if tracheal intubation was not possible after 20 seconds, further boluses of 0.2 mg kg^?1 were given every 20 seconds until intubation was achieved. Induction dose and adverse events (sneezing, twitching, paddling, excitement, apnoea and cyanosis) were recorded; induction quality and intubation conditions were scored and recorded.ResultsThe mean dose of alfaxalone required for induction was similar for groups M and B: 1.2 ± 0.4 mg kg^?1. The mean dose requirement for group MB (0.8 ± 0.3 mg kg^?1) was lower than groups M and B (p < 0.0001). Induction dose was not influenced by temperament or level of sedation. Induction and intubation scores did not differ between treatment groups. Adverse events were noted in 16 dogs; there was no association with treatment group, temperament or level of sedation.Conclusions and clinical relevanceMedetomidine and butorphanol administered in combination reduce the anaesthetic induction dose of alfaxalone compared to either agent alone. This difference should be taken into account when using this combination of drugs in a clinical setting.     

The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse

ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.Study designProspective experimental study.AnimalsTen (five male and five female), adult, healthy, Standardbred horses.MethodsHorses were premedicated with acepromazine (0.03 mg kg^?1 IV). Twenty minutes later they received xylazine (1 mg kg^?1 IV), then after 5 minutes, guaiphenesin (35 mg kg^?1 IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg^?1). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1–5 (1 very poor, 5 excellent).ResultsThe median (range) induction and recovery scores were 4 (3–5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1–5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t_1/2), plasma clearance (Clp) and volume of distribution (V_d) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute^?1 kg^?1 and 1.6 ± 0.4 L kg^?1, respectively.Conclusions and clinical relevanceAlfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.     

Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate

ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate.Study designProspective experimental study.AnimalsFive clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg.MethodsFoals were premedicated with butorphanol (0.05 mg kg^?1 IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg^?1. Cardiorespiratory variables (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and alfaxalone plasma concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis.ResultsThe harmonic, mean ± SD plasma elimination half life (t½) for alfaxalone was 22.8 ± 5.2 minutes. The observed mean plasma clearance (Cl_p) and volume of distribution (Vd) were 19.9 ± 5.9 mL minute kg^?1 and 0.6 ± 0.2 L kg^?1, respectively. Overall, the quality of the anaesthetic inductions and recoveries was good and most monitored physiological variables were clinically acceptable in all foals, although some foals became hypoxaemic for a short period following recumbency. The mean durations of anaesthesia from induction to first movement and from induction to standing were 18.7 ± 7 and 37.2 ± 4.7 minutes, respectively.ConclusionsThe anaesthetic protocol used provided a predictable and consistent plane of anaesthesia in the five foals studied, with minimal cardiovascular depression. In foals, as in the adult horse, alfaxalone has a short elimination half life.Clinical relevanceAlfaxalone appears to be an adequate anaesthetic induction agent in foals and the pharmacokinetics suggest that, with continuous infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen supplementation is recommended.     

The utility of a novel formulation of alfaxalone in a remote delivery system

ObjectiveTo quantify induction time, reliability, physiological effects, recovery quality and dart volume of a novel formulation of alfaxalone (40 mg mL^?1) used in combination with medetomidine and azaperone for the capture and handling of wild bighorn sheep.Study designProspective clinical study.AnimalsA total of 23 wild bighorn sheep (Ovis canadensis) in Sheep River Provincial Park, AB, Canada.MethodsFree-ranging bighorn sheep were immobilized using medetomidine, azaperone and alfaxalone delivered with a remote delivery system. Arterial blood was collected for measurement of blood gases, physiologic variables (temperature, heart and respiratory rates) were recorded and induction and recovery length and quality were scored.ResultsData from 20 animals were included. Administered dose rates were alfaxalone (0.99 ± 0.20 mg kg^?1; 40 mg mL^?1), azaperone (0.2 ± 0.04 mg kg^?1; 10 mg mL^?1) and medetomidine (0.16 ± 0.03 mg kg^?1; 30 mg mL^?1). The mean drug volume injected was 1.51 mL. The median (range) induction time was 7.7 (5.8–9.7) minutes, and recovery was qualitatively smooth.Conclusions and clinical relevanceAn increased concentration formulation of alfaxalone was administered in combination with medetomidine and azaperone, and resulted in appropriate anesthesia for the capture and handling of bighorn sheep. The dart volume was small, with potential for reducing capture-related morbidity.     

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

ObjectiveTo evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses undergoing elective surgery.MethodsAfter sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg^?1 initially, then 2 mg kg^?1 hour^?1) and ketamine (2 mg kg^?1 hour^?1), both CRIs reducing to 1.5 mg kg^?1 hour^?1 after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 μg kg^?1 hour^?1, reducing after 50 minutes to 2.75 μg kg^?1 hour^?1, and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE′ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 μg kg^?1) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05.ResultsFE′ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE′ISO in MILK was 0.65 (0.4–1.0) %, and in ILK was 1 (0.62–1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups.Conclusion and clinical relevanceA CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.